OPTIMAL MEDICAL MANAGEMENT OF CHRONIC HEART FAILURE

Professor Colonel Ni Ni Win

M.B.,B.S(Ygn), M.Med.Sc(Int: Med:) , M.A.C.T.M(Australia)

M.R.C.P(UK), Dr.Med.Sc(Cardiology)F.R.C.P(Edin)

FASCC(Asean),Dip.Med. Education,FACC(USA),FAPSIC

Senior Consultant Cardiologist/Interventionist

Professor/Head,Cardiac Medical Department

Defence Services General Hospital

21-1-2018

Optimal Medical Management of

Chronic Heart Failure

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Definition of Heart Failure

The pathophysiological state in which heart is unable to pump blood at a rate commensurate

with the requirements of metabolizing tissue, or can do so only from an elevated filling pressure

(Braunwald,1994)

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Global Causes of Death

Ischemia + Heart Failure – sinister alliance

Etiology

Coronary Artery DiseaseHTValvular and Congenital Heart DiseaseArrhythmiasCardiomyopathy (dilated, hypertrophic/obstructive/obliIterative)Alcohol and DrugsOthers (anemia, thyrotoxicosis, pulmonary HT, constrictive pericarditpericardial effusion)

account for 70-85% of HF cases

Established and Hypothesized Risk Factors for Heart Failure

• Major Clinical Risk Factors– Age, male sex– Hypertension, LVH– Myocardial infarction– Diabetes Mellitus– Valvular heart disease – Obesity

• Minor Clinical Risk Factors– Smoking– Dyslipidemia– Sleep-disordered breathing– Chronic kidney disease– Albuminuria– Homocysteine– Immune activation, IGF1, TNFα,

IL-6, CRP– Natriuretic peptides– Anemia– Dietary risk factors– Increased HR– Sedentary lifestyle– Low socioeconomic status– Psychological stress

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ACEI trials in Chronic Heart FailureStudy Population Total (n) ACEI ACC Stage Results

CONSENSUS 1 Clinical evidence of severe heart failure

253 Enalapril D 40% RRR in mortality at 6 mo (1°endpoint)50% RRR mortality from worsening heart failure

SOLVD Treatment EF≤35% 2569 Enalapril C 16% RR mortality (1° endpoint)26% combined reduction mortality/hospitalization from progressive heart failure

SOLVD Prevention EF≤35% 4228 Enalapril B Non-significant reduction in all-cause mortality(1° endpoint)20% reduction in combined

incidence of death or heart failure hospitalization

ATLAS EF≤30% 3164 Lisinopril low dose (2.5-5mg) vs high dose (32.5-35mg)

C, likely D 8% non-significant RRR mortality (1°endpoint) 12% RRR mortality + hospitalization in higher dose group.24% RRR heart failure hospitalization

CONSENSUS = Cooperative North Scandinavian Enalapril Survival Study; SOLVD = Studies Of left Ventricular Dysfunction trial:ATLAS = Assessment of Treatment with Lisinopril an Survival trial; EF = ejection fraction; RRR = relative risk reduction; CV = cardiovascular

ACEI trials in Post-MIStudy Population Total (n) ACEI Results

AIRE 3-10 days post-MI.Clinical evidence of heart failure

1986 Ramipril 23% RRR overall mortality (1° endpoint)19% RRR combined death, AMI, worsening heart failure, Stroke

SAVE EF≤ 40% 2231 Captopril 19% RRR overall mortality (1° endpoint)25% RR recurrent MI21% RRR CV mortality

TRACE EF≤ 35%3-7 days post-MI

1749 Trandopril 22% RRR all-cause mortality (1° endpoint)29% reduction in progression of heart failure

GISSI-3 Within 24 hrs of AMI 18895 Lisinopril 11% decrease in mortality at 6 weeks (1°endpoint)

ISIS-4 Within 24 hrs of AMI 58050 Captopril 7% reduction in mortality at 5 weeks (1°endpoint)

CONSENSUS II Within 24 hrs of AMI 6090 Enalapril(Intravenous followed by oral enalapril)

No improvement in survival 6 months post-MI (1° endpoint)

SMILE Within 24 hrs of AMI 1556 Zofenopril 33% RRR in combined death or progression to severe heart faillure at 6 weeks (1° endpoint)29% RRR mortality at 1 year

SAVE = Survival and Ventricular Enlargement; TRACE = Trandopril Cardiac Evaluation Study; GISSI-3 = Gruppo Italian per lo Studiodella Sopravvivenza nell’Infarto Miocardico; ISIS-4 = International Study of Infarct Survival; AIRE – Acute Infarction Ramipril Efficacy triaSMILE = Survival of Myocardial Infarction Long-Term Evaluation; AMI = Acute Myocardial Infarct; EF = ejection fraction; RRR = relative risk reduction; CV= cardiovascular

ACEI in Heart Failure

• ACC/AHA guidelines for management of patients after an ST elevation MI (STEMI) give a class I recommendation for initiation of ACEI therapy within 24 hours of AMI.

• ACC/AHA also give a Class I recommendation for initiating early ACEI therapy in patients with non-STEMI (NSTEMI) or unstable angina who have concomitant persistent hypertension, symptoms of heart failure, LV dysfunction, or diabetes.

ARB trials in Heart Failure (1)

Study Population Total (n) ARB ACC stage

Results

OPTIMAAL Acute-MI and clinical evidence of heart failure EF<35%

5477 Losartan(losartan vs captopril)

B, C, D NS superiority in captopril group for all-cause mortality (1°endpoint)Losartan better tolerated than captopril

VALIANT EF≤35% and/orclinical evidence of heart failure.0.5-10 days post-MI

9818 Valsartan(valsartan vs valsartan + captopril vs captopril)

B, C, D NS for mortality (1° endpoint);SCD; hospitalization).

CHARM-Alternative

EF≤40%Intolerant of ACEI

2028 Candesartan(candesartan vs placebo)

C, D 23% RRR CV death or HF hospitalization (1° endpoint)

ELITE II EF≤40%Age≥60 yr old

3152 Losartan(losartan vs captopril)

C, D NS difference in mortality (1°endpoint) or SCD

OPTIMAAL = Optimal trial in Myocardial Infarction with Angiotensin II Antagonist Losartan; VALIANT = Valsartan in Acute Myocardial InCHARM = Candesartan in Heart Failure; ELITE = Evaluation of Losartan in the Elderly; NS = non-significant; SCD = sudden cardiac de

Beta-blocker trials in HFStudy Population Total

(n)Beta-blocker ACC stage Results

U.S.Carvedilol EF ≤ 40% 1,094 Carvedilol C, D 48% RR heart failure progression (1°endpoint)65% RRR overall mortality27% reduction CV hospitalization

COPERNICUS EF < 25% 2,289 Carvedilol D 35% RRR overall mortality (1° endpoint)

MERIT-HF EF ≤ 40% 3,991 Metoprolol C, D 34% RRR overall mortality (1° endpoint)41% reduction in SCD

CIBIS II EF ≤ 35% 2,647 Bisoprolol C, D 34% RRR overall mortality (1° endpoint)32% RRR death/hospitalization42% RRR sudden cardiac death

REVERT EF < 40% 149 Metoprolol XL B 200mg dose: LVEF ↑ 6%LVESVI ↓ 14 ml/m² (1° endpoint)50mg dose: LVEF ↑ 4%

CAPRICORN EF ≤ 40%3-21 days post-MI

1,959 Carvedilol B, C, D 23% reduction all-cause mortality (1°endpoint)59% reduction atrial arrhythmias70% fewer ventricular arrhythmias

COPERNICUS = Carvedilol Prospective Randomized Cumulative Survival trial; MERIT-HF = Metoprolol CR/XL RandomizedTrial in Congestive Heart Failure; CIBIS – II = Cardiac Insufficiency Bisoprolol Study II; REVERT = Reversal of Ventricular Rewith Toprol-XL; CAPRICORN = Carvedilol Post-Infarct Survival Control in LV Dysfunction;

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ACEI/ARB/B B

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ARNI

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DIGITALIS

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DIURETICS

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CO MOBIDITIES

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ANGINA

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IVABRADINE

Heart rate as a predictor ofHeart rate as a predictor of

CARDIOVASCULAR DEATH

Fox et al. Lancet. 2008;372:817-21.

+ 34%

REVASCULARIZATION

+38%

HOSPITALIZATION FOR HF

HOSPITALIZATION FOR MI

+ 53%

+ 46%

Ranolazine

Trimetazidine

-Blockers

Calcium antag.

Nitrates

Nicorandil

Ivabradine

Improvedtime to onset

of ST-segmentdepression

+

+

+

+

+

+

+

Decreasein anginalepisodes

+

+

+

+

+

+

+

Improvedtotal

exerciseduration

+

+

+

+

+

+

+

Reducedrevascularization

NA

–

–

+

–

NA

+

Preventionof MI

NA

–

–

–

–

–

+

Improvedsurvival

NA

–

–

–

–

–

–

Ivabradine - the only antianginal treatment to reduce myocardial infarction in stable coronary patients

Fox K, et al. Lancet. 2008;372:807-816

Adapted from ESC Guidelines on stable angina 2006

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Metabolic Modulation of IschaemiaMetabolic Modulation of Ischaemia

By shifting cardiac energy metabolism, from FFA to glucose, metabolic agents provide +33%more ATP

Trimetazidine

+33% ATP

Recommendations for treatment of patients with DHF

Recommendation Class Level of Evidence

Physicians should control systolic and diastolic hypertension, in accordance with published guidelines.

I A

Physicians should control ventricular rate in patients with atrial fibrillation. I C

Physicians should use diuretics to control pulmonary congestion and peripheral edema.

I C

Coronary revascularization is reasonable in patients with coronary arterydisease in whom symptomatic or demonstrable myocardial ischemia is judged to be having an adverse effect on cardiac function.

IIa C

Restoration and maintenance of sinus rhythm in patients with atrialfibrillation might be useful to improve symptoms.

IIa C

The use of beta-adrenergic blocking agents, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, or calcium antagonists in patients with controlled hypertension might be effective to minimize symptoms of heart failure.

IIb C

The use of digitalis to minimize symptoms of heart failure is not well established.

IIb C

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TEAM CARE

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FOLLOW UP

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THANK YOU